Genetic lesions associated with chronic lymphocytic leukemia transformation to Richter syndrome.
Genetic lesions associated with chronic lymphocytic leukemia transformation to Richter syndrome.
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DOI：
10.1084/jem.20131448
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发表时间：
2013-10-21
期刊：
影响因子：
--
通讯作者：
Dalla-Favera R
中科院分区：
文献类型：
--
作者：
Fabbri G;Khiabanian H;Holmes AB;Wang J;Messina M;Mullighan CG;Pasqualucci L;Rabadan R;Dalla-Favera R
描述从CLL到RS的克隆进化模式，CLL向RS转化的遗传决定因素，以及RS与经典的非CLL相关的DLBCL之间的致病关系。里希特综合征(RS)源于慢性淋巴细胞白血病(CLL)罕见地转变为侵袭性淋巴瘤，最常见的是弥漫性大B细胞淋巴瘤(DLBCL)类型。目前对RS的分子发病机制尚不完全清楚。通过结合9对CLL-RS对和43例RS病例的完整外显子测序和拷贝数分析，我们发现这种侵袭性疾病典型地起源于占主导地位的CLL克隆，平均获得∼20个遗传损害/病例。就负荷和频谱而言，RS损害在患者之间是不同的，包括那些参与CLL进展和化疗耐药(TP53破坏和NOTCH1激活)的损害，以及一些以前未涉及CLL或RS发病机制的损害。尤其是CDKN2A/B细胞周期调节基因的紊乱与30%的RS患者的∼有关。最后，我们报告了RS和DLBCL的基因组图谱显著不同，这表明它们代表了不同的疾病实体。这些结果为RS的发病机制提供了洞察力，并确定了潜在的诊断和治疗相关性的失调通路。
Characterization of the pattern of clonal evolution from CLL to RS, the genetic determinants of CLL transformation to RS, and the pathogenetic relationship between RS and classical non–CLL-associated de novo DLBCL. Richter syndrome (RS) derives from the rare transformation of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, most commonly of the diffuse large B cell lymphoma (DLBCL) type. The molecular pathogenesis of RS is only partially understood. By combining whole-exome sequencing and copy-number analysis of 9 CLL-RS pairs and of an extended panel of 43 RS cases, we show that this aggressive disease typically arises from the predominant CLL clone by acquiring an average of ∼20 genetic lesions/case. RS lesions are heterogeneous in terms of load and spectrum among patients, and include those involved in CLL progression and chemorefractoriness (TP53 disruption and NOTCH1 activation) as well as some not previously implicated in CLL or RS pathogenesis. In particular, disruption of the CDKN2A/B cell cycle regulator is associated with ∼30% of RS cases. Finally, we report that the genomic landscape of RS is significantly different from that of de novo DLBCL, suggesting that they represent distinct disease entities. These results provide insights into RS pathogenesis, and identify dysregulated pathways of potential diagnostic and therapeutic relevance.
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DOI：
10.1073/pnas.0710052104
发表时间：
2007-12-11
影响因子：
11.1
作者：
Beroukhim, Rameen;Getz, Gad;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
15.3
作者：
DOMEN, J;VANDERLUGT, NMT;BERNS, A
通讯作者：
BERNS, A
影响因子：
64.8
作者：
Berger, Michael F.;Hodis, Eran;Heffernan, Timothy P.;Deribe, Yonathan Lissanu;Lawrence, Michael S.;Protopopov, Alexei;Ivanova, Elena;Watson, Ian R.;Nickerson, Elizabeth;Ghosh, Papia;Zhang, Hailei;Zeid, Rhamy;Ren, Xiaojia;Cibulskis, Kristian;Sivachenko, Andrey Y.;Wagle, Nikhil;Sucker, Antje;Sougnez, Carrie;Onofrio, Robert;Ambrogio, Lauren;Auclair, Daniel;Fennell, Timothy;Carter, Scott L.;Drier, Yotam;Stojanov, Petar;Singer, Meredith A.;Voet, Douglas;Jing, Rui;Saksena, Gordon;Barretina, Jordi;Ramos, Alex H.;Pugh, Trevor J.;Stransky, Nicolas;Parkin, Melissa;Winckler, Wendy;Mahan, Scott;Ardlie, Kristin;Baldwin, Jennifer;Wargo, Jennifer;Schadendorf, Dirk;Meyerson, Matthew;Gabriel, Stacey B.;Golub, Todd R.;Wagner, Stephan N.;Lander, Eric S.;Getz, Gad;Chin, Lynda;Garraway, Levi A.
通讯作者：
Garraway, Levi A.
DOI：
10.1084/jem.20110921
发表时间：
2011-07-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fabbri G;Rasi S;Rossi D;Trifonov V;Khiabanian H;Ma J;Grunn A;Fangazio M;Capello D;Monti S;Cresta S;Gargiulo E;Forconi F;Guarini A;Arcaini L;Paulli M;Laurenti L;Larocca LM;Marasca R;Gattei V;Oscier D;Bertoni F;Mullighan CG;Foá R;Pasqualucci L;Rabadan R;Dalla-Favera R;Gaidano G
通讯作者：
Gaidano G
DOI：
10.1126/science.1229259
发表时间：
2013-02-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Huang FW;Hodis E;Xu MJ;Kryukov GV;Chin L;Garraway LA
通讯作者：
Garraway LA